Higher Cumulative Bortezomib Dose Associated with Longer OS in Multiple Myeloma

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NEW ORLEANSHigher cumulative doses of bortezomib are associated with improved overall survival (OS) among patients with previously untreated multiple myeloma, reported authors of a retrospective analysis of data from the phase 3 VISTA trial. The findings were presented at the 55th American Society of Hematology Annual Meeting and Exposition.

“Although sample size was limited, continued bortezomib treatment following attainment of complete remission may also be associated with improved OS,” reported Maria-Victoria Mateos, MD, PhD, of the University Hospital of Salamanca, in Salamanca, Spain, and coauthors.

There has been little clinical guidance on optimal bortezomib treatment duration, the coauthors noted. “The phase 3 VISTA study demonstrated the superiority of bortezomib-melphalan-prednisone (VMP) versus melphalan-prednisone (MP) in transplant-ineligible patients with previously untreated multiple myeloma in terms of response rates, time to progression, and OS.”

However, the association between patient survival and cumulative bortezomib dose, representing both total dose and time on therapy, have not been assessed, prompting the new analysis.

A total of 340 VISTA study participants received at least one dose of bortezomib, with a median cumulative dose of 39 mg/m2 (range, 1.3-71.2 mg/m2), the coauthors reported. Half the patients (n = 170) received a cumulative dose less than 39 mg/m2, and half received 39 mg/m2 or more of bortezomib.

Patients receiving higher cumulative doses also had longer OS, the researchers found. Median OS was 66.3 versus 46.2 months (hazard ratio [HR]: 0.533; P < 0.0001; adjusted for age and HR: 0.561; P = 0.0002), they reported. Results “were robust when adjusted for differences in baseline characteristics and in the 180-day landmark analysis to account for early deaths,” they noted.

“The group of patients who received lower cumulative bortezomib doses displayed a higher incidence of early treatment discontinuation due to adverse events, patient choice, disease progression, or death as compared to patients in the higher cumulative dose group,” they added.

Approaches to bortezomib maintenance include switching to subcutaneous bortezomib, which is associated with “comparable outcomes and an improved safety profile,” modifying the dose schedule, and “proactively managing adverse events,” the researchers reported.

Previous research indicate that “a less intensive VMP regimen, with limited or no twice-weekly dosing followed by a less dose-intense bortezomib schedule, could be used to achieve a similar cumulative bortezomib dose and thus maximize treatment duration and outcome,” they added.

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